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Phosphorylated insulin-like growth factor-1 receptor (pIGF1R) is a poor prognostic factor in brain metastases from lung adenocarcinomas

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Abstract

A greater understanding of brain metastases is imperative for developing novel therapeutic strategies. Our previous study showed that insulin-like growth factor (IGF) signaling pathway was activated in brain-tropic cancer cells. In this study, we investigated the clinical relevance of activated (phosphorylated) IGF-1 receptor (pIGF1R) expression in brain metastases originating from lung adenocarcinomas. All pathologically confirmed brain metastases from lung adenocarcinomas, with available archived specimens from January 1998 to December 2009 at National Taiwan University Hospital, were assessed immunohistochemically for pIGF1R expression using H-score criteria. A median H-score was used as a cutoff point to define high or low pIGF1R expression. The mutation status in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) was examined using direct sequencing. The prognostic significance of pIGF1R expression, its correlations with clinicopathological characteristics, and EGFR status were evaluated. In the 86 cases, high membranous/cytoplasmic pIGF1R expression in brain metastases correlated with a shorter median survival (10.8 vs 27.8 mo, P = 0.003). This correlation was more significant in patients with EGFR mutations [hazard ratio (HR) 2.38, 95 % confidence interval (CI) 1.19–4.77 for EGFR mutations; HR 1.99, 95 % CI 0.95–4.15 for EGFR wild type] and remained statistically significant in multivariate analysis after adjusting for the effects of other potential prognostic factors, including the graded prognostic assessment score, solitary brain metastasis, extracranial metastatic status, EGFR mutations, and treatment using EGFR tyrosine kinase inhibitors. Although we also identified nuclear pIGF1R expression, this result was prognostically non-significant. Our study results showed that high membranous/cytoplasmic pIGF1R expression in brain metastases was a poor prognostic factor, more significantly in patients with EGFR mutations than in those with wild-type EGFRs.

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References

  1. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322(8):494–500

    Article  PubMed  CAS  Google Scholar 

  2. Jenkinson MD, Haylock B, Shenoy A, Husband D, Javadpour M (2011) Management of cerebral metastasis: evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy. Eur J Cancer 47(5):649–655

    Article  PubMed  Google Scholar 

  3. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B (1998) Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA, J Am Med Assoc 280(17):1485–1489

    Article  CAS  Google Scholar 

  4. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363(9422):1665–1672

    Article  PubMed  Google Scholar 

  5. Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29(2):134–141

    Article  PubMed  Google Scholar 

  6. Flannery TW, Suntharalingam M, Regine WF, Chin LS, Krasna MJ, Shehata MK, Edelman MJ, Kremer M, Patchell RA, Kwok Y (2008) Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery. Int J Radiat Oncol Biol Phys 72(1):19–23

    Article  PubMed  Google Scholar 

  7. Pei-Fang Wu, Ching-Hung Lin, Wen-Chang Huang, Wen-Chi Feng, Yen-Shen Lu, Chih-Hsin Yang, Ann-Lii Cheng (2013) Activated IGF signaling pathway is a potential therapeutic target for brain metastasis from lung cancer. [abstract No. 3886]. Proceedings of the 104th Annual Meeting of the American Association for Cancer Research, AACR Philadelphia, Washington 6–10 April 2013

  8. Law JH, Habibi G, Hu K, Masoudi H, Wang MY, Stratford AL, Park E, Gee JM, Finlay P, Jones HE, Nicholson RI, Carboni J, Gottardis M, Pollak M, Dunn SE (2008) Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Res 68(24):10238–10246

    Article  PubMed  CAS  Google Scholar 

  9. Litzenburger BC, Creighton CJ, Tsimelzon A, Chan BT, Hilsenbeck SG, Wang T, Carboni JM, Gottardis MM, Huang F, Chang JC, Lewis MT, Rimawi MF, Lee AV (2011) High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts correlates with sensitivity to anti-IGF-IR therapy. Clin Cancer Res 17(8):2314–2327

    Article  PubMed  CAS  Google Scholar 

  10. Chakravarty G, Santillan AA, Galer C, Adams HP, El-Naggar AK, Jasser SA, Mohsin S, Mondal D, Clayman GL, Myers JN (2009) Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer. Exp Biol Med (Maywood) 234(4):372–386

    Article  CAS  Google Scholar 

  11. Kim WY, Prudkin L, Feng L, Kim ES, Hennessy B, Lee JS, Lee JJ, Glisson B, Lippman SM, Wistuba II, Hong WK, Lee HY (2012) Epidermal growth factor receptor and K-Ras mutations and resistance of lung cancer to insulin-like growth factor 1 receptor tyrosine kinase inhibitors. Cancer 118(16):3993–4003

    Article  PubMed  CAS  Google Scholar 

  12. Gee JM, Robertson JF, Gutteridge E, Ellis IO, Pinder SE, Rubini M, Nicholson RI (2005) Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer. Endocr Relat Cancer 12(Suppl 1):S99–S111

    Article  PubMed  CAS  Google Scholar 

  13. Sommer J, Itani DM, Homlar KC, Keedy VL, Halpern JL, Holt GE, Schwartz HS, Coffin CM, Kelley MJ, Cates JM (2010) Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential therapeutic targets in chordoma. J Pathol 220(5):608–617

    Article  PubMed  CAS  Google Scholar 

  14. Sandberg-Nordqvist AC, Stahlbom PA, Reinecke M, Collins VP, von Holst H, Sara V (1993) Characterization of insulin-like growth factor 1 in human primary brain tumors. Cancer Res 53(11):2475–2478

    PubMed  CAS  Google Scholar 

  15. Gualco E, Wang JY, Del Valle L, Urbanska K, Peruzzi F, Khalili K, Amini S, Reiss K (2009) IGF-IR in neuroprotection and brain tumors. Front Biosci 14:352–375

    Article  CAS  Google Scholar 

  16. Rohrmann S, Linseisen J, Becker S, Allen N, Schlehofer B, Overvad K, Olsen A, Tjonneland A, Melin BS, Lund E, Vineis P, Grioni S, Tumino R, Palli D, Mattiello A, Bonet C, Chirlaque MD, Sanchez MJ, Rodriguez L, Dorronsoro M, Ardanaz E, Lagiou P, Trichopoulou A, Trichopoulos D, Dossus L, Grote VA, Boeing H, Aleksandrova K, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, Khaw KT, Wareham NJ, Key TJ, Rinaldi S, Romieux I, Gallo V, Michaud DS, Riboli E, Kaaks R (2011) Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev 20(10):2174–2182

    Article  PubMed  CAS  Google Scholar 

  17. Zumkeller W (2002) IGFs and IGF-binding proteins as diagnostic markers and biological modulators in brain tumors. Expert Rev Mol Diagn 2(5):473–477

    Article  PubMed  CAS  Google Scholar 

  18. Lonn S, Rothman N, Shapiro WR, Fine HA, Selker RG, Black PM, Loeffler JS, Hutchinson AA, Inskip PD (2008) Genetic variation in insulin-like growth factors and brain tumor risk. Neuro oncol 10(4):553–559

    Article  PubMed  CAS  Google Scholar 

  19. Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, Glazer PM (1997) Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 57(15):3079–3083

    PubMed  CAS  Google Scholar 

  20. Kalinina T, Bockhorn M, Kaifi JT, Thieltges S, Gungor C, Effenberger KE, Strelow A, Reichelt U, Sauter G, Pantel K, Izbicki JR, Yekebas EF (2010) Insulin-like growth factor-1 receptor as a novel prognostic marker and its implication as a cotarget in the treatment of human adenocarcinoma of the esophagus. Int J Cancer 127(8):1931–1940

    Article  PubMed  CAS  Google Scholar 

  21. Resnik JL, Reichart DB, Huey K, Webster NJ, Seely BL (1998) Elevated insulin-like growth factor I receptor autophosphorylation and kinase activity in human breast cancer. Cancer Res 58(6):1159–1164

    PubMed  CAS  Google Scholar 

  22. Rocha RL, Hilsenbeck SG, Jackson JG, VanDenBerg CL, Weng C, Lee AV, Yee D (1997) Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin Cancer Res 3(1):103–109

    PubMed  CAS  Google Scholar 

  23. Nakamura M, Miyamoto S, Maeda H, Zhang SC, Sangai T, Ishii G, Hasebe T, Endoh Y, Saito N, Asaka M, Ochiai A (2004) Low levels of insulin-like growth factor type 1 receptor expression at cancer cell membrane predict liver metastasis in Dukes’ C human colorectal cancers. Clin Cancer Res 10(24):8434–8441

    Article  PubMed  CAS  Google Scholar 

  24. Taunk NK, Goyal S, Moran MS, Yang Q, Parikh R, Haffty BG (2010) Prognostic significance of IGF-1R expression in patients treated with breast-conserving surgery and radiation therapy. Radiother Oncol 96(2):204–208

    Article  PubMed  CAS  Google Scholar 

  25. Gallardo A, Lerma E, Escuin D, Tibau A, Munoz J, Ojeda B, Barnadas A, Adrover E, Sanchez-Tejada L, Giner D, Ortiz-Martinez F, Peiro G (2012) Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3 K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. Br J Cancer 106(8):1367–1373

    Article  PubMed  CAS  Google Scholar 

  26. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30(4):419–425

    Article  PubMed  Google Scholar 

  27. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70(2):510–514

    Article  PubMed  Google Scholar 

  28. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A, Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M (2010) Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys 77(3):655–661

    Article  PubMed  Google Scholar 

  29. Shih JY, Gow CH, Yu CJ, Yang CH, Chang YL, Tsai MF, Hsu YC, Chen KY, Su WP, Yang PC (2006) Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer. Int J Cancer 118(4):963–969

    Article  PubMed  CAS  Google Scholar 

  30. Wu SG, Gow CH, Yu CJ, Chang YL, Yang CH, Hsu YC, Shih JY, Lee YC, Yang PC (2008) Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma. Eur Respir J 32(4):924–930

    Article  PubMed  CAS  Google Scholar 

  31. Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17(4):343–346

    Article  PubMed  CAS  Google Scholar 

  32. Cappuzzo F, Tallini G, Finocchiaro G, Wilson RS, Ligorio C, Giordano L, Toschi L, Incarbone M, Cavina R, Terracciano L, Roncalli M, Alloisio M, Varella-Garcia M, Franklin WA, Santoro A (2010) Insulin-like growth factor receptor 1 (IGF1R) expression and survival in surgically resected non-small-cell lung cancer (NSCLC) patients. Ann Oncol 21(3):562–567

    Article  PubMed  CAS  Google Scholar 

  33. Dziadziuszko R, Merrick DT, Witta SE, Mendoza AD, Szostakiewicz B, Szymanowska A, Rzyman W, Dziadziuszko K, Jassem J, Bunn PA Jr, Varella-Garcia M, Hirsch FR (2010) Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression. J Clin Oncol 28(13):2174–2180

    Article  PubMed  Google Scholar 

  34. Kim JS, Kim ES, Liu D, Lee JJ, Solis L, Behrens C, Lippman SM, Hong WK, Wistuba II, Lee HY (2012) Prognostic impact of insulin receptor expression on survival of patients with nonsmall cell lung cancer. Cancer 118(9):2454–2465

    Article  PubMed  CAS  Google Scholar 

  35. Ludovini V, Bellezza G, Pistola L, Bianconi F, Di Carlo L, Sidoni A, Semeraro A, Del Sordo R, Tofanetti FR, Mameli MG, Daddi G, Cavaliere A, Tonato M, Crino L (2009) High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients. Ann Oncol 20(5):842–849

    Article  PubMed  CAS  Google Scholar 

  36. Zhao H, Desai V, Wang J, Epstein DM, Miglarese M, Buck E (2012) Epithelial-mesenchymal transition predicts sensitivity to the dual IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines. Mol Cancer Ther 11(2):503–513

    Article  PubMed  CAS  Google Scholar 

  37. Reidy DL, Vakiani E, Fakih MG, Saif MW, Hecht JR, Goodman-Davis N, Hollywood E, Shia J, Schwartz J, Chandrawansa K, Dontabhaktuni A, Youssoufian H, Solit DB, Saltz LB (2010) Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer. J Clin Oncol 28(27):4240–4246

    Article  PubMed  CAS  Google Scholar 

  38. Bodzin AS, Wei Z, Hurtt R, Gu T, Doria C (2012) Gefitinib resistance in HCC mahlavu cells: upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation. J Cell Physiol 227(7):2947–2952

    Article  PubMed  CAS  Google Scholar 

  39. Sehat B, Tofigh A, Lin Y, Trocme E, Liljedahl U, Lagergren J, Larsson O (2010) SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor. Sci signal 3(108):ra10

    Google Scholar 

  40. Warsito D, Sjostrom S, Andersson S, Larsson O, Sehat B (2012) Nuclear IGF1R is a transcriptional co-activator of LEF1/TCF. EMBO Rep 13(3):244–250

    Article  PubMed  CAS  Google Scholar 

  41. Sarfstein R, Pasmanik-Chor M, Yeheskel A, Edry L, Shomron N, Warman N, Wertheimer E, Maor S, Shochat L, Werner H (2012) Insulin-like growth factor-I receptor (IGF-IR) translocates to nucleus and autoregulates IGF-IR gene expression in breast cancer cells. J Biol Chem 287(4):2766–2776

    Article  PubMed  CAS  Google Scholar 

  42. Aleksic T, Chitnis MM, Perestenko OV, Gao S, Thomas PH, Turner GD, Protheroe AS, Howarth M, Macaulay VM (2010) Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells. Cancer Res 70(16):6412–6419

    Article  PubMed  CAS  Google Scholar 

  43. Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, Cassier P, Decouvelaere AV, Ranchere D, Kurtz JE, Bergerat JP, Blay JY (2012) Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer 48(16):3027–3035

    Article  PubMed  CAS  Google Scholar 

  44. Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA, Lynch TJ, Sequist LV (2010) EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro oncol 12(11):1193–1199

    Article  PubMed  CAS  Google Scholar 

  45. Gow CH, Chien CR, Chang YL, Chiu YH, Kuo SH, Shih JY, Chang YC, Yu CJ, Yang CH, Yang PC (2008) Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response. Clin Cancer Res 14(1):162–168

    Article  PubMed  CAS  Google Scholar 

  46. Porta R, Sanchez-Torres JM, Paz-Ares L, Massuti B, Reguart N, Mayo C, Lianes P, Queralt C, Guillem V, Salinas P, Catot S, Isla D, Pradas A, Gurpide A, de Castro J, Polo E, Puig T, Taron M, Colomer R, Rosell R, Mayo C et al (2011) Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 37(3):624–631

    Article  PubMed  CAS  Google Scholar 

  47. Desbois-Mouthon C, Cacheux W, Blivet-Van Eggelpoel MJ, Barbu V, Fartoux L, Poupon R, Housset C, Rosmorduc O (2006) Impact of IGF-1R/EGFR cross-talks on hepatoma cell sensitivity to gefitinib. Int J Cancer 119(11):2557–2566

    Article  PubMed  CAS  Google Scholar 

  48. Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI (2004) Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer 11(4):793–814

    Article  PubMed  CAS  Google Scholar 

  49. Chakravarti A, Loeffler JS, Dyson NJ (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62(1):200–207

    PubMed  CAS  Google Scholar 

  50. Morgillo F, Kim WY, Kim ES, Ciardiello F, Hong WK, Lee HY (2007) Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res 13(9):2795–2803

    Article  PubMed  CAS  Google Scholar 

  51. Hurbin A, Wislez M, Busser B, Antoine M, Tenaud C, Rabbe N, Dufort S, de Fraipont F, Moro-Sibilot D, Cadranel J, Coll JL, Brambilla E (2011) Insulin-like growth factor-1 receptor inhibition overcomes gefitinib resistance in mucinous lung adenocarcinoma. J Pathol 225(1):83–95

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by National Taiwan University Hospital (Grant 101-M2002, 102-M2247).

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Authors and Affiliations

  1. National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei, 100, Taiwan

    Pei-Fang Wu

  2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Rd, Taipei, 100, Taiwan

    Pei-Fang Wu

  3. Department of Pathology, Taipei Medical University-Wan Fang Hospital, No. 111, Section 3, Hsing-Long Rd, Taipei, 116, Taiwan

    Wen-Chang Huang

  4. Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei, 100, Taiwan

    James Chih-Hsin Yang, Yen-Shen Lu, Ching-Hung Lin & Ann-Lii Cheng

  5. Graduate Institute of Oncology, College of Medicine, National Taiwan University, No. 2, Xuzhou Rd, Taipei, 100, Taiwan

    James Chih-Hsin Yang & Ann-Lii Cheng

  6. Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei, 100, Taiwan

    Jin-Yuan Shih & Ann-Lii Cheng

  7. Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, No. 579, Sec. 2, Yunlin Rd, Douliou City, Yun-Lin, 640, Taiwan

    Jin-Yuan Shih & Shang-Gin Wu

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  1. Pei-Fang Wu
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Correspondence to Ching-Hung Lin or Ann-Lii Cheng.

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Wu, PF., Huang, WC., Yang, J.CH. et al. Phosphorylated insulin-like growth factor-1 receptor (pIGF1R) is a poor prognostic factor in brain metastases from lung adenocarcinomas. J Neurooncol 115, 61–70 (2013). https://doi.org/10.1007/s11060-013-1194-3

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